目的探讨新疆地区哈萨克族散发性乳腺癌中BRCA1和BRCA2基因的突变频率及分布情况。方法选择2005年1月-2013年10月新疆医科大学第一附属医院和附属肿瘤医院收治的来自新疆地区的哈萨克族乳腺癌患者86例(病例组)和哈萨克族健康女性70例(对照组),由外周静脉血提取基因组DNA,对乳腺癌易感基因1(Breast Carcinoma 1,BRCA1)外显子2、10、18、20和乳腺癌易感基因2(Breast Carcinoma 2,BRCA2)外显子10、11及外显子-内含子拼接区进行DNA直接测序,并鉴定突变位点。结果病例组和对照组共检测到的18个突变位点中,rs80357374、rs4987117为未知功能变异,其余均为多态性改变。在病例组和对照组中分别检测到195个和143个变异序列。病例组rs1799950、rs1801499、rs1799944的分布频率明显高于对照组,差异有统计学意义(P<0.05)。在中国人群中尚未检测到rs80357374,Intron18-268为新发突变位点,但在对照组中均检测到2个基因突变。两组中携带4个以上突变的患者人数占各组携带者的56.9%、39.6%,差异无统计学意义(P>0.05)。BRCA2突变频率高于BRCA1,但2个基因突变频率差异无统计学意义(P>0.05)。结论哈萨克族乳腺癌患者BRCA1和BRCA2突变频率高,且相当一部分受试对象同时携带多个突变位点,这可能是哈萨克族人群的特有遗传特征。rs1799950、rs1801499、rs1799944这3个位点可能增加哈萨克族人群罹患乳腺癌的风险,值得今后进一步研究验证。 Objective To investigate the frequency and distribution of BRCA1 and BRCA2 mutations in Kazakh sporadic breast cancer in Xinjiang region. Methods From January 2005 to October 2013, 86 cases of Kazakh patients (case group) and 70 healthy Kazakh women (control group) from Xinjiang region were enrolled in the First Affiliated Hospital of Xinjiang Medical University and Affiliated Tumor Hospital. Genomic DNA was extracted from peripheral venous blood and the exons 2, 10, 18, 20 of Breast Carcinoma 1 (BRCA1) and Breast Carcinoma 2 (BRCA2) exons 10,11 and exon-intron splicing region for DNA sequencing and identification of mutation sites. Results Among the 18 mutation sites detected in the case group and the control group, rs80357374 and rs4987117 were unknown functional variation, and the others were all polymorphic changes. In the case group and the control group were detected 195 and 143 variant sequences. The distribution frequencies of rs1799950, rs1801499 and rs1799944 in case group were significantly higher than those in control group (P <0.05). In Chinese population, rs80357374 and Intron18-268 have not been detected, but two mutations were detected in the control group. The number of patients carrying more than 4 mutations in both groups accounted for 56.9% and 39.6% of carriers in each group, the difference was not statistically significant (P> 0.05). The frequency of BRCA2 mutation was higher than that of BRCA1, but there was no significant difference in the frequency of mutation between the two genes (P> 0.05). Conclusion The mutation frequency of BRCA1 and BRCA2 in Kazakh patients with breast cancer is high, and a large number of subjects carry multiple mutation sites at the same time. This may be the characteristic genetic characteristics of Kazakh population. These three sites of rs1799950, rs1801499 and rs1799944 may increase the risk of breast cancer in Kazak population and are worthy of further study and verification in the future.